Transcatheter mitral valve prosthesis

ABSTRACT

A prosthetic cardiac valve comprises an anchor having an atrial skirt, an annular region, and a ventricular skirt. The prosthetic valve also has a plurality of prosthetic valve leaflets each having a first end and a free end. The first end is coupled with the anchor and the free end is opposite the first end. The prosthetic cardiac valve has an open configuration in which the free ends of the prosthetic valve leaflets are disposed away from one another to allow antegrade blood flow therepast, and a closed configuration in which the free ends of the prosthetic valve leaflets engage one another and substantially prevent retrograde blood flow therepast. The anchor has a collapsed configuration for delivery to the heart and an expanded configuration for anchoring the prosthetic cardiac valve to a patient&#39;s heart.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.14/046,606, U.S. Pat. No. 9,770,329), filed Oct. 4, 2013; which is adivisional of U.S. patent application Ser. No. 13/096,572, U.S. Pat. No.8,579,964), filed Apr. 28, 2011; which claims the benefit of U.S.Provisional Patent Applications Nos. 61/414,879 filed Nov. 17, 2010;61/393,860 filed Oct. 15, 2010; and 61/331,799 filed May 5, 2010; theentire contents of which are incorporated herein by reference.

BACKGROUND OF THE INVENTION Field of the Invention

The present invention generally relates to medical devices and methods,and more particularly relates to the treatment of valve insufficiency,such as mitral insufficiency, also referred to as mitral regurgitation.The use of prosthetic valves delivered by traditional surgicalimplantation methods, or by less invasive percutaneous catheter orminimally invasive transapical methods are one possible treatment forvalvar insufficiency.

The heart of vertebrate animals is divided into four chambers, and isequipped with four valves (the mitral, aortic, pulmonary and tricuspidvalves) that ensure that blood pumped by the heart flows in a forwarddirection through the cardiovascular system. The mitral valve of ahealthy heart prevents the backflow of blood from the left ventricleinto the left atrium of the heart, and comprises two flexible leaflets(anterior and posterior) that close when the left ventricle contracts.The leaflets are attached to a fibrous annulus, and their free edges aretethered by subvalvular chordae tendineae to papillary muscles in theleft ventricle to prevent them from prolapsing into the left atriumduring the contraction of the left ventricle.

Various cardiac diseases or degenerative changes may cause dysfunctionin any of these portions of the mitral valve apparatus, causing themitral valve to become abnormally narrowed or dilated, or to allow bloodto leak (i.e. regurgitate) from the left ventricle back into the leftatrium. Any such impairments compromise cardiac sufficiency, and can bedebilitating or life threatening.

Numerous surgical methods and devices have accordingly been developed totreat mitral valve dysfunction, including open-heart surgical techniquesfor replacing, repairing or reshaping the native mitral valve apparatus,and the surgical implantation of various prosthetic devices such asannuloplasty rings to modify the anatomy of the native mitral valve.More recently, less invasive transcatheter techniques for the deliveryof replacement mitral valve assemblies have been developed. In suchtechniques, a prosthetic valve is generally mounted in a crimped stateon the end of a flexible catheter and advanced through a blood vessel orthe body of the patient until the valve reaches the implantation site.The prosthetic valve is then expanded to its functional size at the siteof the defective native valve.

While these devices and methods are promising treatments for valvarinsufficiency, they can be difficult to deliver, expensive tomanufacture, or may not be indicated for all patients. Therefore, itwould be desirable to provide improved devices and methods for thetreatment of valvar insufficiency such as mitral insufficiency. At leastsome of these objectives will be met by the devices and methodsdisclosed below.

2. Description of the Background Art

By way of example, PCT international patent number PCT/US2008/054410(published as PCT international publication no. WO2008/103722), thedisclosure of which is hereby incorporated by reference, describes atranscatheter mitral valve prosthesis that comprises a resilient ring, aplurality of leaflet membranes mounted with respect to the ring so as topermit blood flow therethrough in one direction, and a plurality oftissue-engaging positioning elements movably mounted with respect to thering and dimensioned to grip the anatomical structure of the heart valveannulus, heart valve leaflets, and/or heart wall. Each of thepositioning elements defines respective proximal, intermediate, anddistal tissue engaging regions cooperatively configured and dimensionedto simultaneously engage separate corresponding areas of the tissue ofan anatomical structure, and may include respective first, second, andthird elongate tissue-piercing elements. The valve prosthesis may alsoinclude a skirt mounted with respect to the resilient ring for sealing aperiphery of the valve prosthesis against a reverse flow of blood aroundthe valve prosthesis.

PCT international patent number PCT/US2009/041754 (published as PCTinternational publication no. WO2009/134701), the disclosure of which ishereby incorporated by reference, describes a prosthetic mitral valveassembly that comprises an anchor or outer support frame with a flaredupper end and a tapered portion to fit the contours of the native mitralvalve, and a tissue-based one-way valve mounted therein. The assembly isadapted to expand radially outwardly and into contact with the nativeheart tissue to create a pressure fit, and further includes tensionmembers anchoring the leaflets of the valve assembly to a suitablelocation on the heart to function as prosthetic chordae tendineae.

Also known in the prior art are prosthetic mitral valve assemblies thatutilize a claw structure for attachment of the prosthesis to the heart(see, for example, U.S. patent application publication no. U.S.2007/0016286 to Hermann et al., the disclosure of which is herebyincorporated by reference), as are prosthetic mitral valve assembliesthat rely on the application of axial rather than radial clamping forcesto facilitate the self-positioning and self-anchoring of the prosthesiswith respect to the native anatomical structure.

Another method which has been proposed as a treatment of mitral valveregurgitation is the surgical bow tie method, which recently has beenadapted into a minimally invasive catheter based treatment where animplant is used to clip the valve leaflets together. This procedure ismore fully disclosed in the scientific and patent literature, such as inU.S. Pat. No. 6,629,534 to St. Goar et al., the entire contents of whichare incorporated herein by reference.

Other relevant publications include U.S. Patent Publication No.2011/0015731 to Carpentier et al.

BRIEF SUMMARY OF THE INVENTION

The present invention generally relates to medical devices and methods,and more particularly prosthetic valves used to treat mitralregurgitation. While the present disclosure focuses on the use of aprosthetic valve for treating mitral regurgitation, this is not intendedto be limiting. The prosthetic valves disclosed herein may also be usedto treat other body valves including other heart valves or venousvalves. Exemplary heart valves include the aortic valve, the triscupsidvalve, or the pulmonary valve.

In embodiments of the present subject matter, transcatheter mitral valveprostheses and transcatheter methods and systems of deploying the sameare provided. In certain embodiments, the mitral valve prosthesiscomprises a tissue-type prosthetic one-way valve structure comprising aplurality of leaflets affixed within a self-expanding or expandableanchor (i.e. frame) portion having a geometry that expands into a lowprofile atrial skirt region, an annular region dimensioned to generallyconform to a native mitral valve annulus, a ventricular skirt regionthat displaces the native mitral valve leaflets, and a plurality ofleaflet commissures extending into the sub-annular ventricular space(i.e. in the direction of the outflow of blood through the prosthesis)and configured to optimize the efficiency of the prosthetic valvestructure and the load distribution on the leaflets thereof. The anchorportion may also in preferred embodiments be asymmetrical along itslongitudinal axis, with the atrial skirt region, the annular regionand/or the ventricular skirt region having differently configuredanterior and posterior aspects in order to facilitate closeaccommodation of the asymmetrical contours and features of a typicalnative mitral valve apparatus. This asymmetry may result inherently fromthe structural configuration of the anchor portion as discussed furtherbelow, and/or as a consequence of shaping or forming steps employedduring the manufacturing process.

The prosthetic valve structure in preferred embodiments may comprise abicuspid or tricuspid valve in order, in part, to simplify manufactureof the mitral valve prosthesis, but as would be readily apparent tothose of skill in the art, other configurations are possible. Theleaflets may be fabricated from a single piece or from multiple piecesof standard biologic prosthetic materials, such as cryo- orchemically-preserved pericardium (e.g. bovine, equine, porcine, caprine,kangaroo), or from standard suitable synthetic prosthetic materials(e.g. fiber-reinforced matrix materials) well known in the art, and maybe sewn or otherwise adhered to the anchor to form the valve leaflets inany standard suitable manner.

To optimize prosthetic valve efficiency and the load distribution on theprosthetic leaflets, the commissures extend generally axially in acantilevered fashion downstream into the sub-annular space, and arecapable of flexing radially and laterally along their axial lengths todistribute the forces associated with blood flow through the prostheticvalve structure. In some embodiments, the commissures define (when themitral valve prosthesis is in an expended state) a somewhatfrustoconical aperture that narrows along the forward direction of bloodflow in order to aid in the closure of the prosthetic valve structureduring contraction of the ventricle. To further optimize efficiency andload distribution on the leaflets, the commissures may be shaped anddimensioned so as to provide for the attachment of the leaflets alongarcuate seams, and may also be made selectively flexible at differentpoints or zones along their axial length through, for example, theaddition or deletion of reinforcing struts, or through variation of thethickness of the commissures in selected regions.

The anchor portion of the mitral valve prosthesis is preferablyfabricated from a single piece of metallic material that has been cut soas to permit the mitral valve prosthesis to be compressed into acompact, generally tubular delivery configuration, and expanded into thedeployment configuration further described herein. In self-expandingembodiments, the anchor portion of the mitral valve prosthesis may befabricated from a shape memory alloy (SMA) such as the nickel-titaniumalloy nitinol, and in expandable embodiments, the anchor portion may befabricated from any metallic material, such as chromium alloy orstainless steel, that is suitable for implantation into the body. Insome embodiments, the metallic material may be of a single thicknessthroughout entirety of the anchor portion, and in others may vary inthickness so as to facilitate variations in the radial force that isexerted by the anchor portion in specific regions thereof, to increaseor decrease the flexibility of the anchor portion in certain regions,and/or to control the process of compression in preparation fordeployment and the process of expansion during deployment.

When deployed, the atrial skirt region of the mitral valve prosthesisextends generally radially outwards so as to lie flat against and coverthe atrial surface of the native mitral valve annulus, and to anchor themitral valve prosthesis against at least a portion of the adjoiningatrial surface of the heart. The atrial skirt region has a low axialprofile (extending only slightly into the atrium of the heart) in orderto minimize potentially thrombogenic turbulence in blood flow, and inpreferred embodiments, may be covered with standard biologic orsynthetic prosthetic materials of the sort described above in order toseal the atrial skirt region against the atrial surface and tofacilitate the funnelling of atrial blood through the mitral valveprosthesis. In some embodiments, the atrial skirt region furthercomprises atrial barbs or prongs to further facilitate the anchoring ofthe deployed prosthesis to the atrial heart surface. To facilitate theorientation and alignment of the mitral valve prosthesis within thenative mitral valve upon deployment, particularly in embodiments wherethe anchor portion is longitudinally asymmetrical, the atrial skirtregion of the anchor portion of the mitral valve prosthesis maypreferably further comprise an alignment structure that may bedifferentiated (such as by angiography, computed tomography, etc.) fromthe remainder of the atrial skirt region and thereby used as anorientation guide during deployment. Most preferably, the alignmentstructure may comprise an elongation of the anterior aspect of theatrial skirt region configured to expand radially to accommodate theaortic root portion of the atrial surface.

The annular region of the mitral valve prosthesis is dimensioned, asnoted above, to generally conform to and anchor against a native mitralvalve annulus when deployed. In preferred embodiments, the deployedannular region may define a generally D-shaped annulus suitable forfitting the contours of a typical native mitral valve, and may becovered with standard biologic or synthetic prosthetic materials of thesort previously described to seal the annular region against the nativemitral valve annulus.

The ventricular skirt region expands when deployed in the ventricularspace generally radially outwards against the native mitral valve, butnot so far as to obstruct the left ventricular outflow tract, nor tocontact the ventricular wall. To anchor the mitral valve prosthesisagainst the displaced native leaflets in the ventricular space, themaximal radial displacement of the fully deployed ventricular skirtregion is selected to be slightly greater than the circumference of thenative mitral valve. In preferred embodiments, the ventricular skirtregion also comprises ventricular and/or native leaflet barbs or prongsto further anchor the deployed prosthesis thereto. Most preferably, theventricular skirt region is asymmetrical and the prongs thereof comprisetwo trigonal anchoring tabs located in the anterior aspect of theventricular skirt region for anchoring against the fibrous trigones oneither side of the anterior leaflet of the native mitral valve, and oneposterior ventricular anchoring tab located in the posterior aspect ofthe ventricular skirt region for anchoring over the posterior leaflet ofthe native mitral valve. Associated with these tabs are deploymentcontrol regions as described in further detail below.

The ventricular skirt region may also in some embodiments be coveredwith standard biologic or synthetic prosthetic materials of the sortpreviously described in order to seal the ventricular skirt regionagainst the displaced native leaflets, and thereby to funnel ventricularblood (during contraction of the ventricle) towards the prosthetic valvestructure to assist in the closure thereof during contraction of theventricle.

The combined 3-zone anchoring of the mitral valve prosthesis against theatrial surface, the native valve annulus, and the displaced nativeleaflets (supplemented, in preferred embodiments by a fourth zone ofanchoring from the trigonal and posterior ventricular anchoring) in theventricular space prevents the prosthesis from migrating or dislodgingfrom within the native valve annulus during the contraction of theatrium or the ventricle, and lessens the anchoring pressure that isrequired to be applied in any given anchoring zone as compared to aprosthesis that is anchored in only a single anchoring zone, or in anycombination of these four anchoring zones. The consequent reduction inradial force required to be exerted against the native structures ineach zone minimizes the risk of obstruction or impingement of the nearbyaortic valve or aortic root caused by the displacement of the nativemitral valve apparatus. The combined 3 or 4-zone anchoring of the mitralvalve prosthesis also facilitates the positioning and/or re-positioningof the mitral valve prosthesis as described below.

To deploy the mitral valve prosthesis within the native mitral valveapparatus, the prosthesis is first compacted and loaded into asuitably-adapted conventional catheter delivery system of the sort wellknown to those of skill in the art. Preferably, to facilitate laterdeployment, the commissures and associated prosthetic valve structure ofthe prosthesis are captured within an inner lumen of the catheterdelivery system, and the remaining portions of the anchor region arecaptured within a secondary outer lumen of the catheter delivery system.The loaded mitral valve prosthesis may then be delivered (typicallyeither transseptally or transapically) in its compacted form into theleft atrium of the heart using a conventional catheter delivery system.The prosthesis is releasably attached to the catheter delivery systemvia its commissures, and shielded by the (preferably dual-lumen)delivery sheath thereof during transit into the atrial space. Once theprosthesis has been guided into the left atrium, the delivery sheath ofthe catheter delivery system is retracted as described below in order topermit expansion of the various regions of the prosthesis to proceed. Ofcourse, in self-expanding embodiments, expansion of the prosthesis willoccur spontaneously upon retraction of the delivery sheath, and inexpandable embodiments, a catheter inflation structure such as a balloonis required to effect the expansion.

Deployment of the mitral valve prosthesis may proceed differentlydepending upon the features of the particular embodiment of theprosthesis being deployed. For example, in asymmetrical embodiments thatcomprise trigonal anchoring tabs and a posterior ventricular anchoringtab in the ventricular skirt region (as well as, preferably, analignment structure in the atrial region), these tabs may preferably bedeployed before deployment of the remaining portions of the ventricularskirt regions in order to facilitate the anchoring of these tabs againstthe native fibrous trigones and posterior leaflet, respectively.

In the first general deployment step, the atrial skirt region of themitral valve prosthesis is permitted to expand by retracting thecorresponding portion of the catheter delivery sheath (or isballoon-expanded following the retraction of the corresponding portionof the delivery sheath) within the left atrium of the heart, and theexpanded atrial skirt region is then positioned over the atrial surfaceof the native mitral valve and anchored against at least a portion ofthe adjoining atrial surface of the heart. In preferred embodimentswhere the atrial skirt region comprises an alignment structure, thisfirst general deployment step may be further broken down into twosub-steps, wherein the catheter delivery sheath is first retracted onlyso far as to permit expansion of the alignment structure (so that it maybe visualized to facilitate manipulation of the delivery system in sucha way as to orient the mitral valve prosthesis into a desired position),and then, once initial alignment of the prosthesis appears to besatisfactory, further retracted to permit the expansion, positioning andanchoring of the remaining portions of the atrial skirt region. Inembodiments where the alignment structure comprises an elongation of theanterior aspect of the atrial skirt region, such initial alignmentcomprises the rotation and/or alignment of the alignment structure sothat it is situated adjacent the aortic root and between the fibroustrigones of the native anterior leaflet.

Next, the annular region of the prosthesis is permitted to expand byfurther retraction of the catheter delivery sheath so as to engage thenative mitral valve annulus (i.e. to contact the native valve annulusthroughout at least a majority thereof) in order to create a secondanchoring zone and to create a suitable opening for blood flow throughthe prosthetic valve structure.

Then, in embodiments that comprise trigonal anchoring tabs and aposterior ventricular anchoring tab in the ventricular skirt region, thecatheter delivery sheath is further retracted so far as to permit thetabs to expand while the remainder of the ventricular skirt region ofthe prosthesis, including the deployment control regions of the tabs,remain sheathed. With the deployment control regions still retainedwithin the delivery system and the atrial skirt region anchored againstthe atrial surface, the tabs project radially outward to facilitateengagement with the corresponding features of the native mitral valve.The posterior ventricular anchoring tab is aligned in the middle of theposterior leaflet of the mitral valve where there is an absence ofchordae attachments to the posterior leaflet, and passed over theposterior leaflet to seat between the posterior leaflet and theventricular wall. The two trigonal anchoring tabs are positioned oneither side of the anterior leaflet with their heads positioned at thefibrous trigones. Slight rotation and realignment of the prosthesis canoccur at this time.

Once the assembly has been satisfactorily positioned and the tabsaligned, the catheter delivery sheath may be further retracted to permitexpansion of the remaining portions of the ventricular skirt region tosecure the prosthesis within the mitral apparatus and seal the mitralannulus. Complete retraction of the outer catheter delivery sheathreleases the ventricular skirt region and allows the anchoring tabs toproximate their anchoring location. As the prosthesis expands, thetrigonal tabs anchor against the fibrous trigones, capturing the nativeanterior leaflet and chordae between the tabs and the anterior surfaceof the prosthetic valve assembly, and the posterior ventricular tabanchors between the ventricular wall and the posterior leaflet,capturing the posterior leaflet between the posterior anchoring tab andthe posterior surface of the prosthetic valve assembly. The remainingportions of the ventricular skirt region expand out against the nativemitral valve leaflets and adjacent anatomy, thereby creating a sealingfunnel within the native leaflets and displacing the native leafletsfrom the prosthetic commissures to avoid obstruction of the prostheticvalve function. With the commissures of the prosthesis still capturedwithin the delivery system, very minor adjustments may still made toensure accurate positioning, anchoring and sealing.

In embodiments that do not comprise trigonal anchoring tabs and aposterior ventricular anchoring tab in the ventricular skirt region, theretraction of the catheter delivery sheath from the ventricular skirtregion may, of course, be performed in one step after the atrial skirtand annular regions of the prosthesis have been initially anchored, topermit the ventricular skirt region of the prosthesis to expand againstthe native mitral valve, and to additionally anchor the prosthesisagainst the displaced native leaflets in the ventricular space.Optionally, the mitral valve prosthesis, which is still at this pointreleasably attached to the catheter delivery system via its commissures,may be driven slightly further downstream into ventricular space tocreate a greater seating force as between the atrial skirt region andatrial surface of the heart, and to provide additional purchase for anyventricular and/or native leaflet barbs or prongs that may be present inthe ventricular skirt region. In embodiments where one or more of theatrial skirt region, the annular region and the ventricular skirt regionare covered with a suitable biologic or synthetic prosthetic material, aseal may also be formed between the respective regions of the prosthesisand the associated zone of the native mitral valve apparatus.

Finally, once satisfactory positioning of the prosthesis has beenachieved, the commissures are released from the catheter deliverysystem, allowing the catheter delivery system to be withdrawn, andleaving the mitral valve prosthesis in place as a functional replacementfor the native mitral valve apparatus. Upon release of the commissures,the prosthesis may further undergo a final stage of foreshortening andseating as any remaining pressure exerted by the delivery system isreleased. The atrial skirt region may recoil slightly from this releasein pressure, pulling the prosthesis slightly further up in to the leftatrium, and thereby further seating the ventricular skirt region,including any associated barbs, prongs or tabs. In embodiments thatcomprise trigonal anchoring tabs, the seating thereof pulls the capturedanterior leaflet tightly against the prosthesis, thereby avoiding orminimizing obstruction of the Left Ventricular Outflow Tract (LVOT), andfirmly seats the ventricular skirt region in the annulus to preventparavalvular leakage. Once final deployment is complete, the deliverysystem is retracted and removed.

In a first aspect of the present invention, a method of anchoring aprosthetic valve in a patient's heart comprises providing the prostheticvalve, wherein the prosthetic valve comprises an anchor having an atrialskirt, an annular region, a ventricular skirt, and a plurality of valveleaflets, wherein the anchor has a collapsed configuration for deliveryto the heart and an expanded configuration for anchoring with the heart,and positioning the prosthetic valve in the patient's heart. The methodalso comprises expanding the atrial skirt radially outward so as to lieover a superior surface of the patient's native mitral valve, anchoringthe atrial skirt against a portion of the atrium, and radially expandingthe annular region of the anchor to conform with and to engage thenative mitral valve annulus. The method also comprises radiallyexpanding the ventricular skirt thereby displacing the native mitralvalve leaflets radially outward.

At least a portion of the prosthetic valve may be covered with tissue ora synthetic material. Positioning the prosthetic valve may comprisetransseptally delivering the prosthetic valve from the right atrium tothe left atrium of the heart, or transapically delivering the prostheticvalve from a region outside the heart to the left ventricle of theheart.

Expanding the atrial skirt may comprise slidably moving a restrainingsheath away from the atrial skirt thereby allowing radial expansionthereof. The atrial skirt may self-expand when the restraining sheath isremoved therefrom. The method may further comprise applying a force onthe prosthetic valve to ensure that the atrial skirt engages thesuperior surface of the mitral valve. The atrial skirt may comprise aplurality of barbs, and expanding the atrial skirt may compriseanchoring the barbs into the superior surface of the mitral valve.Expanding the atrial skirt may comprise sealing the atrial skirt againstthe superior surface of the native mitral valve.

Radially expanding the annular region may comprise slidably moving arestraining sheath away from the annular region thereby allowing radialexpansion thereof. The annular region may self-expand when therestraining sheath is removed therefrom. Radially expanding the annularregion may comprise asymmetrically expanding the annular region suchthat an anterior portion of the annular region is substantially flat,and a posterior portion of the annular region is cylindrically shaped.

The ventricular skirt may further comprise a trigonal anchoring tab onan anterior portion of the ventricular skirt, and radially expanding theventricular skirt may comprise anchoring the trigonal anchoring tabagainst a first fibrous trigon on a first side of the anterior leafletof the native mitral valve. The native anterior leaflet and adjacentchordae tendineae may be captured between the trigonal anchoring tab andan anterior surface of the anchor. The ventricular skirt may furthercomprise a second trigonal anchoring tab on the anterior portion of theventricular skirt, and wherein radially expanding the ventricular skirtmay comprise anchoring the second trigonal anchoring tab against asecond fibrous trigon opposite the first fibrous trigon. The nativeanterior leaflet and adjacent chordae tendineae may be captured betweenthe second trigonal anchoring tab and an anterior surface of the anchor.The ventricular skirt may further comprise a posterior ventricularanchoring tab on a posterior portion of the ventricular skirt. Radiallyexpanding the ventricular skirt may comprise anchoring the posteriorventricular anchoring tab over a posterior leaflet of the native mitralvalve to seat between the posterior leaflet and a ventricular wall ofthe heart. Radially expanding the ventricular skirt may compriseslidably moving a restraining sheath away from the ventricular skirtthereby allowing radial expansion thereof. The ventricular skirt mayself-expand when the restraining sheath is removed therefrom.

The ventricular skirt may comprise a plurality of barbs, and expandingthe ventricular skirt may comprise anchoring the barbs into hearttissue. The prosthetic valve may comprise a plurality of prostheticvalve leaflets, and radially expanding the ventricular skirt maycomprise displacing the native mitral valve leaflets radially outwardthereby preventing interference of the native mitral valve leaflets withthe prosthetic valve leaflets. Radially expanding the ventricular skirtmay comprise displacing the native mitral valve leaflets radiallyoutward without contacting a ventricular wall, and without obstructing aleft ventricular outflow tract. Radially expanding the ventricular skirtmay comprise asymmetrically expanding the ventricular skirt such that ananterior portion of the ventricular skirt is substantially flat, and aposterior portion of the ventricular skirt is cylindrically shaped.

The atrial skirt may comprise an alignment element, and the method maycomprise aligning the alignment element relative to the patient's valve.The valve may comprise a mitral valve, and aligning may comprisealigning the alignment element with an aortic root and disposing thealignment between two fibrous trigones of an anterior leaflet of themitral valve. Aligning may comprise rotating the prosthetic valve. Theprosthetic valve may comprise a plurality of prosthetic leaflets coupledto one or more commissures, and the method may comprise releasing thecommissures from a delivery catheter. The prosthetic valve may comprisea tricuspid leaflet configuration.

The prosthetic valve may have an open configuration in which theprosthetic valve leaflets are disposed away from one another, and aclosed configuration in which the prosthetic valve leaflets engage oneanother. Blood flows freely through the prosthetic valve in the openconfiguration, and retrograde blood flow across the prosthetic valve issubstantially prevented in the closed configuration. The method maycomprise reducing or eliminating mitral regurgitation. The prostheticvalve may comprise a therapeutic agent, and the method may compriseeluting the therapeutic agent from the prosthetic valve into adjacenttissue.

In another aspect of the present invention, a prosthetic cardiac valvecomprises an anchor having an atrial skirt, an annular region, and aventricular skirt. The anchor has a collapsed configuration for deliveryto the heart and an expanded configuration for anchoring the prostheticcardiac valve to a patient's heart. The prosthetic valve also comprisesa plurality of prosthetic valve leaflets, each of the leaflets having afirst end and a free end, wherein the first end is coupled with theanchor and the free end is opposite of the first end. The prostheticcardiac valve has an open configuration in which the free ends of theprosthetic valve leaflets are disposed away from one another to allowantegrade bloodflow therepast, and a closed configuration in which thefree ends of the prosthetic valve leaflets engage one another andsubstantially prevent retrograde bloodflow therepast.

At least a portion of the atrial skirt may be covered with tissue or asynthetic material. The atrial skirt may further comprise a plurality ofbarbs coupled thereto, the plurality of barbs adapted to anchor theatrial skirt into a superior surface of the patient's mitral valve. Theatrial skirt may comprise a collapsed configuration and an expandedconfiguration. The collapsed configuration may be adapted for deliveryto the patient's heart, and the expanded configuration may be radiallyexpanded relative to the collapsed configuration and adapted to lie overa superior surface of the patient's native mitral valve, therebyanchoring the atrial skirt against a portion of the atrium. The atrialskirt may self-expand from the collapsed configuration to the radiallyexpanded configuration when unconstrained. The atrial skirt may compriseone more radiopaque markers. The atrial skirt may comprise a pluralityof axially oriented struts connected together with a connector elementthereby forming a series of peaks and valleys. Some of the peaks andvalleys may extend axially outward further than the rest of the atrialskirt, thereby forming an alignment element.

At least a portion of the annular region may be covered with tissue or asynthetic material. The annular region may have a collapsedconfiguration and an expanded configuration. The collapsed configurationmay be adapted for delivery to the patient's heart, and the expandedconfiguration may be radially expanded relative to the collapsedconfiguration and adapted to conform with and to engage the nativemitral valve annulus. The annular region may self-expand from thecollapsed configuration to the expanded configuration whenunconstrained. The annular region may comprise an asymmetricallyD-shaped cross-section having a substantially flat anterior portion, anda cylindrically shaped posterior portion. The annular region maycomprise a plurality of axially oriented struts connected together witha connector element thereby forming a series of peaks and valleys. Oneor more of the axially oriented struts may comprise one or more sutureholes extending therethrough, the suture holes sized to receive asuture.

At least a portion of the ventricular skirt may be covered with tissueor a synthetic material. The ventricular skirt may comprise anasymmetrically D-shaped cross-section having a substantially flatanterior portion, and a cylindrically shaped posterior portion. Theventricular skirt may have a collapsed configuration and an expandedconfiguration. The collapsed configuration may be adapted for deliveryto the patient's heart, and the expanded configuration may be radiallyexpanded relative to the collapsed configuration and adapted to displacethe native mitral valve leaflets radially outward. The ventricular skirtmay self-expand from the collapsed configuration to the expandedconfiguration when unconstrained.

The ventricular skirt may further comprise a trigonal anchoring tabdisposed on an anterior portion of the ventricular skirt. The trigonalanchoring tab may be adapted to being anchored against a first fibroustrigon on a first side of an anterior leaflet of the patient's mitralvalve. Thus, the anterior leaflet and adjacent chordae tendineae may becaptured between the trigonal anchoring tab and an anterior surface ofthe anchor. The ventricular skirt may further comprise a second trigonalanchoring tab that may be disposed on the anterior portion of theventricular skirt. The second trigonal anchoring tab may be adapted tobeing anchored against a second fibrous trigon opposite the firstfibrous trigon, such that the anterior leaflet and adjacent chordaetendineae are captured between the second trigonal anchoring tab and theanterior surface of the anchor. The ventricular skirt may furthercomprise a posterior ventricular anchoring tab disposed on a posteriorportion of the ventricular skirt. The posterior ventricular anchoringtab may be adapted to being anchored over a posterior leaflet of thepatient's mitral valve, such that the posterior ventricular anchoringtab is seated between the posterior leaflet and a ventricular wall ofthe patient's heart. The ventricular skirt may further comprise aplurality of barbs coupled thereto, and that may be adapted to anchorthe ventricular skirt into heart tissue. The ventricular skirt maycomprise a plurality of struts connected together with a connectorelement thereby forming a series of peaks and valleys. The one or morestruts may comprise one or more suture holes extending therethrough, andthat may be sized to receive a suture.

The plurality of prosthetic valve leaflets may comprise a tricuspidleaflet configuration. At least a portion of the one or more prostheticvalve leaflets may comprise tissue or a synthetic material. One or moreof the plurality of prosthetic valve leaflets may be disposed over oneor more commissure posts or struts that are radially biased inwardrelative to the ventricular skirt. The one or more commissure posts orstruts may comprise one or more suture holes extending therethrough andthat may be sized to receive a suture. The one or more prosthetic valveleaflets may be coupled to a commissure post or strut having acommissure tab adapted to releasably engage the commissure post or strutwith a delivery device.

The prosthetic cardiac valve may further comprise an alignment elementcoupled to an anterior portion of the anchor. The alignment element maybe adapted to be aligned with an aortic root of the patient's heart anddisposed between two fibrous trigones of an anerior leaflet of thepatient's mitral valve. The alignment element may be coupled with theatrial skirt. The prosthetic cardiac valve may further comprise atherapeutic agent coupled thereto, and adapted to being controllablyeluted therefrom.

In still another aspect of the present invention, a delivery system fordelivering a prosthetic cardiac valve to a patient's heart comprises aninner guidewire shaft having a lumen extending therethrough and adaptedto slidably receive a guidewire, and a hub shaft concentrically disposedover the inner guidewire shaft. The delivery system also comprises abell shaft slidably and concentrically disposed over the hub shaft, asheath slidably and concentrically disposed over the bell shaft, and ahandle near a proximal end of the delivery system. The handle comprisesan actuator mechanism adapted to advance and retract the bell shaft andthe sheath.

The system may further comprise the prosthetic cardiac valve which maybe housed in the sheath in a radially collapsed configuration. Theprosthetic cardiac valve may comprise an anchor having an atrial skirt,an annular region, and a ventricular skirt. The prosthetic valve mayalso comprise a plurality of prosthetic valve leaflets. Each of theleaflets may have a first end and a free end. The first end may becoupled with the anchor and the free end may be opposite of the firstend. The prosthetic cardiac valve may have an open configuration inwhich the free ends of the prosthetic valve leaflets are disposed awayfrom one another to allow antegrade bloodflow therepast. The valve mayhave a closed configuration in which the free ends of the prostheticvalve leaflets engage one another and substantially prevent retrogradeblood flow therepast.

Proximal retraction of the sheath relative to the bell shaft may removea constraint from the prosthetic cardiac valve thereby allowing theprosthetic cardiac valve to self-expand into engagement with thepatient's native heart tissue. The prosthetic cardiac valve may bereleasably coupled with the hub shaft, and proximal retraction of thebell shaft relative to the hub shaft may release the prosthetic cardiacvalve therefrom. The actuator mechanism may comprise a rotatable wheel.The system may further comprise a tissue penetrating distal tip coupledto the hub shaft. The tissue penetrating distal tip may be adapted topass through and expand an incision in the patient's heart. The systemmay further comprise a pin lock mechanism releasably coupled with thehandle. The pin lock mechanism may limit proximal retraction of thesheath.

These and other embodiments are described in further detail in thefollowing description related to the appended drawing figures.

BRIEF DESCRIPTION OF THE DRAWINGS

In the drawings, like reference numerals designate like or similar stepsor components.

FIG. 1 is a schematic illustration of the left ventricle of a heartshowing blood flow during systole with arrows.

FIG. 2 is a schematic illustration of the left ventricle of a hearthaving prolapsed leaflets in the mitral valve.

FIG. 3 is a schematic illustration of a heart in a patient sufferingfrom cardiomyopathy where the heart is dilated and the leaflets do notmeet.

FIG. 3A shows, normal closure of the leaflets.

FIG. 3B shows abnormal closure in the dilated heart.

FIG. 4 illustrates mitral valve regurgitation in the left ventricle of aheart having impaired papillary muscles.

FIGS. 5A-5B illustrate the mitral valve.

FIG. 6 illustrates a bottom, partial cross-sectional view of anexemplary prosthetic mitral valve.

FIG. 7 is a perspective view of the anchor portion of the prostheticmitral valve seen in FIG. 6.

FIG. 8A is a perspective view of a prosthetic mitral valve.

FIG. 8B is a top view from the atrium of the prosthetic valve in FIG.8A.

FIG. 9A illustrates a perspective view of the prosthetic valve in FIG.8A from the atrium.

FIG. 9B illustrates a perspective view of the prosthetic valve in FIG.8A from the ventricle.

FIG. 10 illustrates the prosthetic valve of FIG. 8A uncovered andunrolled in a flat pattern.

FIG. 11 is a side view of a delivery device for implantation of aprosthetic valve.

FIG. 12 is a perspective exploded view of a proximal portion of thedelivery device in FIG. 11.

FIG. 13 is a perspective exploded view of a distal portion of thedelivery device in FIG. 11.

FIG. 14 is a cross-section of the a proximal portion of the deliverydevice in FIG. 11.

FIGS. 15A-15C are cross-sectional views of a distal portion of thedelivery device in FIG. 11.

FIG. 16 is a side view of another exemplary embodiment of a deliverydevice for implantation of a prosthetic valve.

FIG. 17 is a perspective view of the delivery device in FIG. 16.

FIG. 18 is a perspective exploded view of the delivery device in FIG.16.

FIGS. 19A-19B are side views of the delivery device in FIG. 16 duringvarious stages of operation.

FIG. 20 illustrates a distal portion of the delivery device in FIG. 16that is adapted to engage a portion of a prosthetic valve.

FIG. 21 illustrates engagement of the delivery device in FIG. 16 withthe prosthetic valve of FIG. 8A.

FIGS. 22A-22G illustrate an exemplary method of transapically deliveringa prosthetic mitral valve.

FIGS. 23A-23G illustrate an exemplary method of transseptally deliveringa prosthetic mitral valve.

FIG. 24 illustrates a prosthetic mitral valve implanted in the mitralspace.

FIG. 25 illustrates a bottom view of a mitral valve implanted in themitral space looking upward from the left ventricle.

DETAILED DESCRIPTION OF THE INVENTION

Specific embodiments of the disclosed device, delivery system, andmethod will now be described with reference to the drawings. Nothing inthis detailed description is intended to imply that any particularcomponent, feature, or step is essential to the invention.

Cardiac Anatomy. The left ventricle LV of a normal heart H in systole isillustrated in FIG. 1. The left ventricle LV is contracting and bloodflows outwardly through the aortic valve AV, a tricuspid valve in thedirection of the arrows. Back flow of blood or “regurgitation” throughthe mitral valve MV is prevented since the mitral valve is configured asa “check valve” which prevents back flow when pressure in the leftventricle is higher than that in the left atrium LA. The mitral valve MVcomprises a pair of leaflets having free edges FE which meet evenly toclose, as illustrated in FIG. 1. The opposite ends of the leaflets LFare attached to the surrounding heart structure along an annular regionreferred to as the annulus AN. The free edges FE of the leaflets LF aresecured to the lower portions of the left ventricle LV through chordaetendineae CT (also referred to herein as the chordae) which include aplurality of branching tendons secured over the lower surfaces of eachof the valve leaflets LF. The chordae CT in turn, are attached to thepapillary muscles PM which extend upwardly from the lower portions ofthe left ventricle and interventricular septum IVS.

Referring now to FIGS. 2-4, a number of structural defects in the heartcan cause mitral prolapse since inadequate tension is transmitted to theleaflet via the chordae. While the other leaflet LF1 maintains a normalprofile, the two valve leaflets do not properly meet and leakage fromthe left ventricle LV into the left atrium LA will occur, as shown bythe arrow.

Regurgitation also occurs in the patients suffering from cardiomyopathywhere the heart is dilated and the increased size prevents the valveleaflets LF from meeting properly, as shown in FIG. 3. The enlargementof the heart causes the mitral annulus to become enlarged, making itimpossible for the free edges FE to meet during systole. The free edgesof the anterior and posterior leaflets normally meet along a line ofcoaptation C as shown in FIG. 3A, but a significant gap G can be left inpatients suffering from cardiomyopathy, as shown in FIG. 3B.

Mitral valve regurgitation can also occur in patients who have sufferedischemic heart disease where the functioning of the papillary muscles PMis impaired, as illustrated in FIG. 4. As the left ventricle LVcontracts during systole, the papillary muscles PM do not contractsufficiently to effect proper closure. The leaflets LF1 and LF2 thenprolapse, as illustrated. Leakage again occurs from the left ventricleLV to the left atrium LA, as shown by the arrow.

FIG. 5A more clearly illustrates the anatomy of a mitral valve MV whichis a bicuspid valve having an anterior side ANT and a posterior sidePOST. The valve includes an anterior (aortic) leaflet AL and a posterior(mural) leaflet PL. Chordae tendineae CT couple the valve leaflets AL,PL with the antero-lateral papillary muscle ALPM and the postero-medialpapillary muscle PMPM. The valve leaflets AL, PL join one another alonga line referred to as the antero-lateral commissure ALC and theposterior-medial commissure PMC. The annulus AN circumscribes the valveleaflets, and two regions adjacent an anterior portion of the annulus,on opposite sides of the anterior leaflet are referred to as the leftfibrous trigone LFT and also the right fibrous trigone RFT. These areasare indicted by generally by the solid triangles. FIG. 5B more clearlyillustrates the left and right fibrous trigones, LFT, RFT.

While various surgical techniques as well as implantable devices havebeen proposed and appear to be promising treatments for mitralregurgitation, surgical approaches can require a lengthy recoveryperiod, and implantable devices have varying clinical results.Therefore, there still is a need for improved devices and methods fortreating mitral regurgitation. While the embodiments disclosed hereinare directed to an implantable prosthetic mitral valve for treatingmitral regurgitation, one of skill in the art will appreciate that thisis not intended to be limiting, and the device and methods disclosedherein may also be used to treat other cardiac valves such as thetricuspid valve, aortic valve, pulmonary valve, etc, as well as othervalves in the body such as venous valves.

Prosthetic Valve. Prosthetic valves have been surgically implanted inthe heart as a treatment for mitral regurgitation. Some of these valveshave been valves harvested from animals such as porcine valves, andothers have been prosthetic mechanical valves with or without a tissuecovering. More recently, minimally invasive catheter technology has beenused to deliver prosthetic valves to the heart. These valves typicallyinclude an anchor for securing the valve to the patient's heart, and avalve mechanism, either a mechanical valve, a valve with animal tissue,or combinations thereof. The prosthetic valve once implanted, takes overfor malfunctioning native valve, thereby reducing or eliminating valvarinsufficiency. While some of these valves appear promising, there stillis a need for improved valves. The following discloses exemplaryembodiments of a prosthetic valve, a delivery system for the prostheticvalve, and methods of delivering the valve that overcome some of thechallenges associated with existing prosthetic valves.

Referring now to FIGS. 6-7, exemplary embodiments of a mitral valveprosthesis generally designated with reference numeral 10 comprisetricuspid tissue-type prosthetic one-way valve structure 12 comprisingleaflets 14 affixed within self-expanding or expandable anchor portion16 having a geometry that expands into low profile atrial skirt region18, annular region 20, ventricular skirt region 22, and a plurality ofleaflet commissures 24 (also referred to herein as commissure posts)extending axially in a cantilevered fashion downstream into thesub-annular space defined by ventricular skirt region 22. FIG. 6 shows apartial cross-section of the valve 10 from the patient's left ventriclelooking upward toward the right atrium. The atrial skirt region 18 isanchored to a lower portion of the right atrium 19. The valve leaflets14 have an open position (not illustrated) and a closed positionillustrated in FIG. 6. In the open position, the leaflets 14 aredisplaced away from one another to allow blood flow therepast, and inthe closed position, the leaflets 14 engage one another to close thevalve and prevent retrograde blood flow therepast. The valve commissures24 may be configured to optimize the efficiency of the prosthetic valvestructure 12 and the load distribution on the leaflets 14 by providingfor the attachment of the leaflets 14 along arcuate seams 28 (best seenin FIG. 7), and by being made selectively flexible at different pointsor zones along their axial length through the addition/deletion ofreinforcing struts.

FIG. 7 shows a perspective view of the anchor portion 16 of the valve 10which has been formed from a series of interconnected struts. The atrialskirt region 18 forms an annular flanged region on the anchor to helpsecure an upper portion of the prosthetic valve in the atrium, and theannular region 20 is a cylindrical region for anchoring the valve alongthe native valve annulus. The ventricular skirt region 22 similarly iscylindrically shaped and helps anchor a lower portion of the valve inthe patient's left ventricle. Any portion, or all of the anchor may becovered with tissue such as pericardium or other tissues disclosedherein, or a synthetic material such as Dacron or ePTFE may be used tocover the anchor. The covering helps to seal the anchor to the nativevalve, and this helps funnel blood into and through the prostheticvalve, rather than around the valve. In some embodiments, the anchor mayremain uncovered. The prosthetic valve has an expanded configuration anda collapsed configuration. The collapsed configuration has a low profilecylindrical shape that is suitable for mounting on a delivery system anddelivery is preferably made either transluminally on a catheter, ortransapically through the heart wall. The expanded configuration (asillustrated) allow the prosthetic valve to be anchored into a desiredposition.

FIG. 8A illustrates a perspective view of a preferred embodiment of aprosthetic mitral valve with optional coverings removed to allowvisibility of the anchor struts. FIG. 8B illustrates a top view of theprosthetic valve in FIG. 8A from the atrium looking down into theventricle. The valve 800 includes an asymmetrical expanded anchorportion having a D-shaped cross-section. As shown, the anchor portiongenerally comprises anterior 802 and posterior 804 aspects along thelongitudinal axis thereof, as well as atrial 806, annular 808 andventricular 810 regions that correspond generally to the atrial skirt18, annular 20 and ventricular skirt 22 regions of the embodimentdescribed above in FIGS. 6-7. Commissures (also referred to herein ascommissure posts) 813 also correspond generally to the leaflets 14 ofthe embodiment in FIGS. 6-7. The prosthetic valve 800 has a collapsedconfiguration and an expanded configuration. The collapsed configurationis adapted to loading on a shaft such as a delivery catheter fortransluminal delivery to the heart, or on a shaft for transapicaldelivery through the heart wall. The radially expanded configuration isadapted to anchor the valve to the patient's native heart adjacent thedamaged valve. In order to allow the valve to expand from the collapsedconfiguration to the expanded configuration, the anchor portion of thevalve may be fabricated from a self-expanding material such as a nickeltitanium alloy like nitinol, or it may also be made from spring temperstainless steel, or a resilient polymer. In still other embodiments, theanchor may be expandable with an expandable member such as a balloon. Inpreferred embodiments, the anchor is fabricated by laser cutting,electrical discharge machining (EDM), or photochemically etching a tube.The anchor may also be fabricated by photochemically etching a flatsheet of material which is then rolled up with the opposing ends weldedtogether.

The atrial skirt portion 816 forms a flanged region that helps to anchorthe prosthetic valve to the atrium, above the mitral valve. The atrialskirt includes a plurality of triangular fingers which extend radiallyoutward from the anchor to form the flange. The posterior 804 portion ofthe atrial skirt 816 is generally round or circular, while a portion ofthe anterior 802 part of the atrial skirt 816 is flat. Thus, the atrialskirt region preferably has a D-shaped cross-section. This allows theprosthetic valve to conform to the patient's cardiac anatomy withoutobstructing other portions of the heart, as will be discussed below.Each triangular finger is formed from a pair of interconnected struts.The triangular fingers of the atrial skirt generally are bent radiallyoutward from the central axis of the prosthetic valve and lie in a planethat is transverse to the valve central axis. In some embodiments, theatrial skirt lies in a plane that is substantially perpendicular to thecentral axis of the valve. The anterior portion 802 of the atrial skirt806 optionally includes an alignment element 814 which may be one ormore struts which extend vertically upward and substantially parallel tothe prosthetic valve. The alignment element 814 may include radiopaquemarkers (not illustrated) to facilitate visualization under fluoroscopy.The alignment element helps the physician to align the prosthetic valvewith the native mitral valve anatomy, as will be discussed later.

Disposed under the atrial skirt region is the annular region 820 whichalso has a collapsed configuration for delivery, and an expandedconfiguration for anchoring the prosthetic valve along the native valveannulus. The annular region is also comprised of a plurality ofinterconnected struts that form a series of cells, preferably closed.Suture holes 821 in some of the struts allow tissue or other coverings(not illustrated) to be attached to the annular region. Covering all ora portion of the anchor with tissue or another covering helps seal theanchor against the heart valve and adjacent tissue, thereby ensuringthat blood is funneled through the valve, and not around it. The annularregion may be cylindrical, but in preferred embodiments has a posteriorportion 804 which is circular, and an anterior portion 802 which isflat, thereby forming a D-shaped cross-section. This D-shapedcross-section conforms better to the native mitral valve anatomy withoutobstructing blood flow in other areas of the heart.

The lower portion of the prosthetic valve includes the ventricular skirtregion 828. The ventricular skirt region also has a collapsedconfiguration for delivery, and an expanded configuration for anchoring.It is formed from a plurality of interconnected struts that form aseries of cells, preferably closed, that can radially expand. Theventricular skirt in the expanded configuration anchors the prostheticvalve to the ventricle by expanding against the native mitral valveleaflets. Optional barbs 823 in the ventricular skirt may be used tofurther help anchor the prosthetic valve into the ventricular tissue.Barbs may optionally also be included in the atrial skirt portion aswell as the annular region of the anchor. Additionally, optional sutureholes 821 in the ventricular skirt may be used to help suture tissue oranother material to the ventricular skirt region, similarly as discussedabove. The anterior 802 portion of the ventricular skirt may be flat,and the posterior 804 portion of the ventricular skirt may be circular,similarly forming a D-shaped cross-section to anchor and conform to thenative anatomy without obstructing other portions of the heart. Also,the lower portions of the ventricular skirt serve as deployment controlregions since the lower portions can remain sheathed therebyconstraining the ventricular skirt from radial expansion until after theoptional ventricular trigonal tabs and posterior tab have expanded, aswill be explained in greater detail below.

The ventricular skirt portion may optionally also include a pair ofventricular trigonal tabs 824 on the anterior portion of the anchor(only 1 visible in this view) for helping to anchor the prosthetic valveas will be discussed in greater detail below. The ventricular skirt mayalso optionally include a posterior tab 826 on a posterior portion 804of the ventricular skirt for anchoring the prosthetic valve to aposterior portion of the annulus. The trigonal tabs 824 or the posteriortab 826 are tabs that extend radially outward from the anchor, and theyare inclined upward in the upstream direction.

The actual valve mechanism is formed from three commissures posts (alsoreferred to as commissures) 813 which extend radially inward toward thecentral axis of the anchor in a funnel or cone-like shape. Thecommissures 813 are formed from a plurality of interconnected strutsthat create the triangular shaped commissures. The struts of thecommissures may include one or more suture holes 821 that allow tissueor a synthetic material to be attached to the commissures. In thisexemplary embodiment, the valve is a tricuspid valve, therefore itincludes three commissures 813. The tips of the commissures may includea commissure tab 812 (also referred to as a tab) for engaging a deliverycatheter. In this embodiment, the tabs have enlarged head regionsconnected to a narrower neck, forming a mushroom-like shape. Thecommissures may be biased in any position, but preferably angle inwardslightly toward the central axis of the prosthetic valve so thatretrograde blood flow forces the commissures into apposition with oneanother to close the valve, and antegrade blood flow pushes thecommissures radially outward, to fully open the valve. FIG. 8B is a topview illustrating the prosthetic valve of FIG. 8A from the atrial side,and shows the preferred D-shaped cross-section.

FIG. 9A illustrates the prosthetic mitral valve of FIGS. 8A-8B with acovering 870 coupled to portions of the anchor with suture 872. Thisview is taken from an atrial perspective. In this embodiment, thecovering is preferably pericardium which may come from a number ofsources as disclosed elsewhere in this specification. In alternativeembodiments, the covering may be a polymer such as Dacron polyester,ePTFE, or another synthetic material. The covering is preferablydisposed over the annular region 820 and the ventricular skirt region828, and in some embodiments the anterior ventricular trigonal 824 tabsand the ventricular posterior tab 830 may also be covered with the sameor a different material. The covering helps seal the anchor against theadjacent tissue so that blood funnels through the valve mechanism. Inthis embodiment, the atrial skirt is left uncovered, as well as tabs824, 830. Additionally, radiopaque markers 814 a form a portion of thealignment element and facilitate visualization of the prosthetic valveunder fluoroscopy which is important during alignment of the valve.

FIG. 9B is a perspective view of the prosthetic mitral valve seen inFIG. 9A, as seen from the ventricle. The struts of the valve commissuresare covered with the same material or a different material as theannular and ventricular regions as discussed above, thereby forming thetricuspid valve leaflets 813. FIG. 9B shows the valve in the closedconfiguration where the three leaflets are engaged with one anotherpreventing retrograde blood flow. Commissure tabs 812 remain uncoveredand allow the commissures to be coupled with a delivery device as willbe explained below. The prosthetic valve in FIGS. 9A-9B may besterilized so they are suitable for implantation in a patient usingmethods known in the art.

FIG. 10 illustrates the prosthetic valve of FIG. 9A with the coveringremoved, and the remaining anchor unrolled and flattened out. Theprosthetic valve 800 is formed from a plurality of interconnectedstruts. For example, the atrial skirt region 806 includes a plurality ofinterconnected struts that form a series of peaks and valleys. The flatanterior region 802 of the prosthetic valve has its peaks and valleysaxially offset from those of the remaining portion of the atrial skirt,and this region becomes a part of the alignment element 814. Radiopaquemarkers 814 a are disposed on either side of the offset peaks andvalleys and help with visualization during implantation of the valve. Anaxially oriented connector joins the struts of the skirt region 806 withthe struts of the annular region 808. The annular region is alsocomprised of a plurality of axially oriented and interconnected strutsthat form peaks and valleys. Connector struts couple struts of theannular region with the struts of the ventricular region 810. Theventricular region also includes a plurality of interconnected strutsthat form peaks and valleys. Additionally, the struts form the leafletcommissures 813, the ventricular skirt 828, as well as the trigonal andposterior tabs 824, 830. Suture holes 821 are disposed along the strutsof the annular region as well as the ventricular region to allowattachment of a cover such as pericardium or a polymer such as Dacron orePTFE. Barbs 823 are disposed along the ventricular skirt 828 to helpanchor the prosthetic valve to adjacent tissue. Commissure tabs or tabs812 are disposed on the tips of the commissures 813 and may be used toreleasably couple the prosthetic valve with a delivery system as will bedescribed below. One of skill in the art will appreciate that a numberof strut geometries may be used, and additionally that strut dimensionssuch as length, width, thickness, etc. may be adjusted in order toprovide the anchor with the desired mechanical properties such asstiffness, radial crush strength, commissure deflection, etc. Therefore,the illustrated geometry is not intended to be limiting.

Once the flat anchor pattern has been formed by EDM, laser cutting,photochemical etching, or other techniques known in the art, the anchoris radially expanded into a desired geometry. The anchor is then heattreated using known processes to set the shape. Thus, the anchor may beloaded onto a delivery catheter in a collapsed configuration andconstrained in the collapsed configuration with a constraining sheath.Removal of the constraining sheath will allow the anchor to self-expandinto its unbiased pre-set shape. In other embodiments, an expandablemember such as a balloon may be used to radially expand the anchor intoits preferred expanded configuration.

Delivery Systems. FIGS. 11-15C show a delivery apparatus 1124 fashionedto deliver a prosthetic mitral valve to the heart transapically.However, one of skill in the art will appreciate that the deliverysystem may be modified and relative motion of the various componentsadjusted to allow the device to be used to deliver a prosthetic mitralvalve transseptally. The delivery apparatus is generally comprised of ahandle 1101 that is the combination of a handle section 1102 and ahandle section 1103 (best seen in FIG. 12), as well as a flexible tip1110 that can smoothly penetrate the apex of the heart, and a sheathcatheter 1109 which houses several additional catheters that aredesigned to translate axially and will be described in detail below.

The handle 1101 includes a female threaded luer adaptor 1113 whichconnects to a Tuohy Borst adaptor 1114 in order to provide a hemostaticseal with a 0.035″ diameter guide wire (not shown). The female threadedluer adaptor 1113 is in threaded contact with the proximal section ofthe handle 1101 through a threaded port 1131 (best seen in FIG. 12).

As can be seen in FIG. 11, the handle 1101 provides location for thecontrol mechanisms used to position and deploy a prosthetic mitralvalve. The handle 1101 provides housing for a thumbwheel 1106 that canbe accessed through a window 1137 that appears on both the top andbottom of the handle 1101. The thumbwheel 1106 internally mates with athreaded insert 1115 (best seen in FIG. 12) that actuates the sheathcatheter 1109, and the mechanics of this interaction will be explainedin detail below.

FIG. 11 also shows a deployment thumbwheel 1104 that provides lineartranslation to a deployment catheter 1120 (best seen in FIG. 12) whenturned, since the turning motion of the deployment thumbwheel 1104 actsas a power screw, pushing the peg 1128 forward and distally from theuser. The mechanics behind the peg 1128 will be further detailed below.The thumbwheel lock 1105 provides a security measure against unwantedrotation of the deployment thumbwheel 1104 by acting as a physicalbarrier to rotation. In order to turn the deployment thumbwheel 1104 theuser must push forward the thumbwheel lock 1105, disengaging it from twoslots 1147 (seen in FIG. 12) in the deployment thumbwheel 1105.

As can also be seen in FIG. 11, a bleed valve 1108 and fluid line 1107are connected to an internal mechanism in the distal portion of thehandle 1101, which provides a hemostatic seal for the sheath catheter1109. The details of this connection will be described below.

Internal mechanics of the delivery apparatus 1124 are illustrated indetail in FIG. 12, and the following descriptions will reveal theinteractions between individual components, and the manner in whichthose components combine in order to achieve a prosthetic heart valvedelivery apparatus.

As seen in FIG. 12, a handle section 1103 and handle section 1102combine to create a handle 1101 that forms the basis of the deliveryapparatus 1124. In order to advance the sheath catheter 1109 duringvalve loading, or retract the sheath catheter 1109 during deployment, arotatable thumbwheel 1106 is in threaded contact (internal threads 1129seen in FIG. 14) with a threaded insert 1115 (external threads 1130 ofFIG. 13) that translates linearly along the axis of the deliveryapparatus, from a proximal position to a distal position. The sheathcatheter 1109 is in mating contact with the threaded insert 1115 and isfastened through the use of a collar 1117 that aligns and mates thecollar with the insert. The collar 1117 is fastened with screws 1116(best seen in DETAIL A in FIG. 14) to the threaded insert 1115 andcontains a fluid port 1142 (best seen in DETAIL A in FIG. 14) thatprovides location for the fluid line 1117 so that hemostasis can bemaintained between the patient and delivery apparatus. An O-ring 1118(best seen in DETAIL A in FIG. 14) seals the stationary catheter 1119(best seen in FIG. 14) against the sheath catheter 1109. The fluid line1107 also provides a means of visually locating the sheath catheter 1109with respect to position, as a slot 1138 in the handle 1101 allows thefluid line 1107 to translate with the sheath catheter 1109 (through ahole 1151 (best seen in DETAIL A in FIG. 14) during operation, and thistranslation is highly visible. In order to prevent rotation of thethreaded insert during translation, a flat face 1164 has been machinedonto both sides of the threaded insert 1115. The flat faces 1164 remainin contact with bosses 1139 and 1140 that are located on both handlesection 1102 and handle section 1103 so that the bosses 1139 and 1140act to grip the threaded insert 1115 and prevent rotation. A texturedpattern 1155 allows the user to easily turn the thumbwheel 1106 in thesurgical field. Detents 1141 (best seen in FIG. 14) locate flanges 63(seen in FIG. 14) on the thumbwheel 1116 in order to allow for rotation.

The manner in which individual catheters (there are four catheters) movewith respect to each other is illustrated in FIG. 12. Sheath catheter1109 provides housing for the stationary catheter 1119, which in turnprovides housing for the movable hub catheter 1120. The hub catheter1120 translates linearly with respect to the nose catheter 1121 whichcan also be translated with respect to each previous catheter, and thehandle 1101. The stationary catheter 1119 is mated to a handle section1103 in an internal bore 1150 which also forms a seal between thestationary catheter 1119 and the hub catheter 1120. The distal portionof the stationary catheter 1119 is formed in the shape of a bell 1122(see DETAIL A in FIG. 15A) which acts as a housing to retain the hubcapture 1123 (seen in DETAIL A in FIG. 15A).

As previously stated a thumbwheel lock 1105 prevents rotation of thedeployment thumbwheel 1104. In order to provide a seating force thatkeeps the thumbwheel lock 1105 in a locked position until manipulated, aspring 1125 is housed in an internal bore 62 (best seen in FIG. 14) andabuts against a shoulder 1161 (best seen in FIG. 14) that is locatedinside the thumbwheel lock 1105. This spring 1125 maintains the leadingedge 1149 of the thumbwheel lock 1105 in a locked position within thetwo slots 1147 of the deployment thumbwheel 1104. Gripping texture 1154is provided on the thumbwheel lock 1105 for ease of use. In order tolocate and retain the thumbwheel lock 1105 inside of the handle 1101, aslot 1135 has been provided in both a handle section 1102 and a handlesection 1103.

As shown in FIG. 12, a sliding block 1127 is housed inside of flatparallel faces 1134 which appear on the inside of the handle 1101. Thissliding block 1127 is in mating contact with hub catheter 1120 and isthe physical mechanism that linearly actuates the catheter. A spring1126 is mounted on an external post 1159 and abuts against a shoulder1133 that is located on the distal end of the sliding block 1127. Thisspring 1126 forces a peg 1128 (located inside a thru-hole 1156 of FIG.14) into contact with the proximal edge of an angled slot 1148 that iscut into the deployment thumbwheel 1104. The deployment thumbwheel 1104is contained between a shoulder 1136 and a snap ring (not shown), bothof which are features of the handle 1101. Gripping texture 1153 on thedeployment thumbwheel 1104 allows the user to easily rotate thethumbwheel in a clockwise direction, actuating the peg 1128 to ridedistally along the slot 1148 and move the sliding block 1127, whichpushes the hub catheter 1120 and hub 1123 (best seen in DETAIL A of FIG.15A) forward and out of the bell 1122 (seen in DETAIL A of FIG. 15A). Aslot 1132 appears in a handle section 1102 and a handle section 1103 andprevents the peg 1128 from translating beyond a desired range.

A nose catheter 1121 extends from a Tuohy Borst adaptor 1114 on theproximal end of the handle 1101, and internally throughout the handleand the respective catheters (sheath catheter 1109, stationary catheter1119, and hub catheter 1120), terminating inside the rigid insert 1112(seen in FIG. 15A) of the flexible tip 1110 (seen in FIG. 15A) thatabuts with the distal end of the sheath catheter 1109.

FIG. 13 displays an exploded view of the tip section of the deliveryapparatus 1124, and shows the relation between prosthetic mitral valve1165 and the internal and external catheters. When crimped and loaded,the prosthetic mitral valve 1165 is encased between the internal surfaceof the sheath catheter 1109 and the external surface of the nosecatheter 1121. In order to capture and anchor the prosthetic mitralvalve 1165 within the delivery apparatus 1124, three commissure tabs1160 (circumferentially spaced at 120.degree. apart) appearing on theproximal end of the prosthetic mitral valve 1165 provide points ofcontact between the valve and three slots 1143 (seen in FIG. 15A) thatare machined into the outer surface of the hub 1123 (circumferentiallyspaced at 120.degree. apart). After first advancing the hub catheter1120 (FIG. 15A) by rotating the deployment thumbwheel 1104 (seen in FIG.12) clockwise, the three commissure tabs 1160 can be captured within thethree slots 1143 (seen in FIG. 15A). The hub 1123 can then be retractedinto the bell 1122 by releasing the deployment thumbwheel 1104 (seen inFIG. 12). In this position the prosthetic mitral valve 1165 is anchoredto the delivery apparatus 1124, and further crimping of the valve willallow the sheath catheter 1109 to be advanced over the valve.

FIGS. 15A-15C further detail the manner in which loading of theprosthetic mitral valve 1165 (seen in FIG. 13) into the deliveryapparatus 1124 can be achieved. Initially, the flexible tip 1110 isabutted against the distal edge 1157 of the sheath catheter 1109. Theflexible tip 1110 is comprised of a rigid insert 1112, and a soft andflexible tip portion 1111 which is over-molded onto the rigid insert1112. The shoulder 1145 and tapered face 1146 of the rigid insert 1112act to guide and locate the distal edge 1157 of the sheath catheter1109, so that the catheter may rest against and be stiffened by theflexible tip 1110, and be more easily introduced into the apex of theheart.

An initial position from which loading can be achieved is illustrated inFIG. 15A. As a first step in the loading of a prosthetic mitral valve1165 (seen in FIG. 13) into the delivery apparatus 1124, the sheathcatheter 1109 is withdrawn by rotation of the thumbwheel 1106 in aclockwise direction. The distal edge 1157 of the sheath catheter 1109 isretracted until it passes the distal edge of the bell 1122, asillustrated in DETAIL A of FIG. 15B. As a second step in the loading ofa prosthetic mitral valve 1165 (seen in FIG. 13) into the deliveryapparatus 1124, the hub 1123 is advanced from beneath the bell 1122 byclockwise turning of the deployment thumbwheel 1104 (seen in FIG. 12),as illustrated in DETAIL A of FIG. 15C. The deployment thumbwheel mayonly be turned once the thumbwheel lock 1105 (see FIG. 12) has been setin the forward position, disengaging it from contact with thethumbwheel. Advancement of the hub 1123 uncovers three slots 1143 intowhich three commissure tabs 1160 of the prosthetic mitral valve 1165(seen in FIG. 13) will fit and be anchored. After anchoring of thecommissure tabs 1160 into the slots 1143 by retraction of the hub 1123has been achieved, a third step in the loading of a prosthetic mitralvalve 1165 (seen in FIG. 13) into the delivery apparatus 1124 may beperformed. The prosthetic mitral valve 1165 (seen in FIG. 13) can becrimped down to a minimum diameter by a loading mechanism (not shown),and then the sheath cannula 1109 can be advanced forward so as to coverthe valve, by rotation of the thumbwheel 1106 in a counter-clockwisedirection. The delivery apparatus 1124 and prosthetic mitral valve 1165are then ready for deployment.

FIGS. 16-19B illustrate another exemplary embodiment of a deliverydevice for implanting a prosthetic valve in the heart transapically.However, one of skill in the art will appreciate that the deliverysystem may be modified and relative motion of the various componentsadjusted to allow the device to be used to deliver a prosthetictransseptally. The delivery apparatus is generally comprised of a handle1601 that is the combination of two halves (1610 and 1635), as well as atip 1603 that can smoothly penetrate the apex of the heart, and aflexible sheath 1602 which is comprised of concentric catheters that aredesigned to translate axially and will be described in detail below.

The handle 1601 includes a handle cap 1611 which connects to a femalethreaded luer adaptor 1612 in order to provide a sealable exit for a0.035″ diameter guide-wire (not shown). The handle cap 1611 is attachedto the handle 1601 with threaded fasteners 1613. The female threadedluer adaptor 1612 is in threaded contact with the handle cap 1611through a tapped port, and when fully inserted squeezes against ano-ring (1636 best seen in FIG. 18) which seals against the outerdiameter of a guide-wire catheter (1621 best seen in FIG. 18).

As can be seen in FIG. 17, the handle 1601 provides location for thecontrol mechanisms used to position and deploy a prosthetic mitralvalve. The handle 1601 provides housing for a thumbwheel 1616 that canbe accessed through a window 1606 that appears on both the top andbottom of the handle 1601. The thumbwheel 1616 internally mates with athreaded insert (1627 in FIG. 18) that actuates the sheath catheter1604, and the mechanics of this interaction will be explained in detailbelow.

FIG. 17 also shows a first hemostasis tube 1617 that is insertedinternally through a slot 1605, and that mates with a first hemo-portthrough a hole (1625 and 1626 in FIG. 18 respectively). The firsthemostasis tube 1617 allows for fluid purging between internalcatheters. The position of the first hemostasis tube 1617 along the slot1605 provides a visual cue as to the position of the sheath catheter1604, and relative deployment phase of a prosthetic mitral valve (notshown). The relationship between the connection of the first hemostasistube 1617 and the sheath catheter 1604 will be described below.

As can also be seen in FIG. 17, a second hemostasis tube 1614 isinserted into the handle 1601 and mated to a second hemo-port (1629 inFIG. 18) in order to allow fluid purging between internal catheters, anddetails of this insertion will be described below. Finally, a pin lock1608 provides a security measure against premature release of aprosthetic mitral valve, by acting as a physical barrier to translationbetween internal mechanisms. Pin lock prongs 1615 rely on spring forceto retain the pin lock 1608 in the handle 1601, and a user must firstpull out the pin lock 1608 before final deployment of a prostheticvalve.

FIG. 17 also shows how the handle 1601 is fastened together by use ofthreaded fasteners and nuts (1607 and 1639 of FIG. 18 respectively), andcountersunk locator holes 1609 placed throughout the handle length.

Internal mechanisms of the delivery system are illustrated in detail inFIG. 18, and the following descriptions will reveal the interactionsbetween individual components, and the manner in which those componentscombine in order to create a system that is able to deliver a prostheticmitral valve preferably transapically.

As seen in FIG. 18, the flexible sheath 1602 is comprised of fourconcentrically nested catheters. In order from smallest to largest indiameter, the concentrically nested catheters will be described indetail. The innermost catheter is a guide-wire catheter 1621 that runsinternally throughout the entire delivery system, beginning at the tip1603 and terminating in the female threaded luer adaptor 1612. Theguide-wire catheter 1621 is composed of a lower durometer, single lumenPebax extrusion and is stationary. It provides a channel through which aguide-wire (not shown) can communicate with the delivery system. Thenext catheter is the hub catheter 1622 which provides support for thehub 1620 and is generally comprised of a higher durometer, single lumenPEEK extrusion. The hub catheter 1622 is in mating connection with boththe hub 1622 at the distal end, and a stainless steel support rod 1634at the proximal end. The stainless steel support rod 1634 is held fixedby virtue of a stopper 1637 that is encased in the handle 1601. The hubcatheter 1622 is stationary, and provides support and axial rigidity tothe concentrically nested catheters. The next catheter is the bellcatheter 1624, which provides housing to the hub 1620 and is generallycomprised of a medium durometer, single lumen Pebax extrusion, includinginternal steel braiding and lubricious liner, as well as a radiopaquemarker band (not shown). The bell catheter 1624 translates axially, andcan be advanced and retracted with respect to the hub 1620. The bellcatheter 1624 is in mating connection with the second hemo-port 1629 atthe proximal end, and hemostasis between the bell catheter 1624 and thestainless steel support rod 1634 can be achieved by purging the secondhemostasis tube 1614. The bell catheter 1624 is bumped up to a largerdiameter 1623 on the distal end in order to encapsulate the hub 1620.The outermost and final catheter is the sheath catheter 1604 whichprovides housing for a prosthetic mitral valve (not shown), and which isable to penetrate the apex of the heart (not shown), by supporting anddirecting a tip 1603 and assisting in the dilation of an incision in theheart wall muscle. The sheath catheter 1604 is generally comprised of amedium durometer, single lumen Pebax extrusion, including internal steelbraiding and lubricious liner, as well as radiopaque marker band (notshown). The sheath catheter 1604 translates axially, and can be advancedand retracted with respect to the hub 1620. The sheath catheter 1604 isin mating connection with the first hemo-port 1625 at the proximal end,and hemostasis between the sheath catheter 1604 and the bell catheter1624 can be achieved by purging the first hemostasis tube 1617.

As seen in FIG. 18, the proximal end of the sheath catheter 1604 is inmating contact with a first hemo-port 1625. The first hemo-port is inmating contact with a threaded insert 1627, and an o-ring 1638, which isentrapped between the first hemo-port 1625 and the threaded insert 1627in order to compress against the bell catheter 1624, creating ahemostatic seal. As the thumbwheel 1616 is rotated, the screw insert1627 will translate, and the sheath catheter 1624 can be retracted oradvanced by virtue of attachment. In order to provide adequate stiffnessto dilate heart wall tissue, the distal edge of the sheath catheter 1604will abut against a shoulder 1618 located on the tip 1603. Thiscommunication allows the tip 1603 to remain secure and aligned with thesheath catheter 1604 during delivery, and creates piercing stiffness.

FIG. 18 also details the mechanism through which the bell catheter 1624can be retracted or advanced with respect to the hub 1620. Thethumbwheel 1616 can be rotated to such an extent that the screw insert1627 will be brought into contact with two pins 1628 that are press fitinto the second hemo-port 1629. As the bell catheter 1624 is in matingcontact with the second hemo-port 1629, further rotation of thethumbwheel 1616 will cause the second hemo-port 1629 to translate andpress against a spring 1633 by virtue of connection to a secondhemo-port cap 1632. This advancement will cause the bumped largerdiameter section 1623 of the bell catheter 1624 to be retracted from thehub 1620. As the thumbwheel 1616 is rotated in the opposite direction,restoring force produced by the spring 1633 will cause the secondhemo-port 1629 to be pushed in the opposite direction, drawing thebumped larger diameter section 1623 of the bell catheter 1624 back overthe hub 1620, an action that is necessary during the initial loading ofa valve prosthesis.

FIG. 18 further details the manner in which hemostasis is achievedbetween the stainless steel support rod 1634 and the bell catheter 1624.An o-ring 1631 is compressed between the second hemo-port 1629 and thesecond hemo-port cap 1632, creating a seal against the stainless steelsupport rod 1634. Hemostasis between the bell catheter 1624 and thestainless steel support rod 1634 can be achieved by purging the secondhemostasis tube 1614, which is in communication with the void to bepurged through a slot and hole 1630.

The deployment process and actions necessary to activate the mechanismsresponsible for deployment are detailed in FIGS. 19A-19B. When performedin the reverse order, these actions also necessitate the first loadingof a valve (not shown) prior to surgery.

As seen in FIG. 19A, manipulation of the thumbwheel 1616 will providetranslational control of the sheath catheter 1604. In order to effectthe deployment of a heart valve (not shown), the user must withdraw thesheath catheter 1604 from contact with the shoulder 1618 of the tip 1603until it passes the larger diameter section 1623 of the bell catheter1624. A heart valve (not shown) will reside concentrically above theguide-wire catheter 1621 in the position indicated by the leader for1621 in FIG. 19A, similarly as to the embodiment illustrated in FIG. 13.The sheath catheter 1604 can be withdrawn until the screw insert 1627comes into contact with the pin lock 1608. The pin lock 1608 must thenbe removed before further travel of the screw insert 1627 can beachieved.

As seen in FIG. 19B, the pin lock 1608 is removed from the handle 1601in order to allow further translation of the sheath catheter 1604. Whenthe sheath catheter 1604 is fully retracted, the larger diameter section1623 of the bell catheter 1624 is also fully retracted, which completelyfrees the heart valve (not shown) from the delivery system. Three hubslots 1619, spaced circumferentially at 120.degree. from each otherprovide the anchoring mechanism and physical link between deliverysystem and heart valve. Once the larger diameter section 1623 of thebell catheter 1624 has been withdrawn, the hub slots 1619 becomeuncovered which allows the heart valve anchor (not shown) to fullyexpand.

FIG. 20 illustrates a distal portion of the delivery device in FIG. 16.Three hub slots 1619 are slidably disposed distally relative to thelarge diameter tip 1623 of bell catheter 1624. These slots allowengagement with a prosthetic valve. The valve may be releasably held bythe slots by disposing the commissure tabs or tabs 812 of the prostheticvalve into slots 1619 and then retracting the slots 1619 under tip 1623of bell catheter 1624. The prosthetic valve may be released from thedelivery catheter by advancing the slots distally relative to the bellcatheter so that the loading anchors or tabs 812 may self-expand out ofand away from slots 1619 when the constraint of tip 1623 on bellcatheter 1624 has been removed.

FIG. 21 illustrates a prosthetic mitral valve 800 (as discussed abovewith reference to FIG. 8A) with the anchor tabs 812 disposed in the hubslots (not visible), and bell catheter 1623 advanced thereover. Thus,even though most of the prosthetic valve 800 has self-expanded into itsexpanded configuration, the valve commissures remain in a collapsedconfiguration with the tabs 812 captured in slots 1619. Once theconstraint provided by bell catheter 1623 has been removed from theslots 1619, the tabs 812 may self-expand out of slots 1619, thecommissures will open up to their unbiased position. The prostheticvalve is then disconnected and free from the delivery device.

Transapical Delivery Methods. FIGS. 22A-22G illustrate an exemplarymethod of transapically delivering a prosthetic mitral valve. Thisembodiment may use any of the prosthetic valves described herein, andmay use any of the delivery devices described herein. FIG. 22Aillustrates the general transapical pathway that is taken with entryinto the heart at the apex 2202, through the left ventricle 2204, acrossthe mitral valve 2206 and into the left atrium 2208. The aortic valve2210 remains unaffected. Transapical delivery methods have beendescribed in the patent and scientific literature, such as inInternational PCT Publication No. WO2009/134701, the entire contents ofwhich are incorporated herein by reference.

In FIG. 22B a delivery device 2214 is introduced through an incision inthe apex 2202 and over a guidewire GW through the ventricle 2204, pastthe mitral valve 2206 with a distal portion of the delivery device 2214disposed in the atrium 2208. The delivery device has a rounded tip 2212that is configured to pass through and dilate the incision, and can beadvanced through the heart without causing unwanted trauma to the mitralvalve 2206 or adjacent tissue. Suture 2216 may be stitched around thedelivery device 2214 at the apex 2202 using a purse string stitch orother patterns known in the art in order to prevent excessive bleedingand to help hold the delivery device in position.

In FIG. 22C, the outer sheath 2214 a of the delivery device 2214 isretracted proximally relative to the prosthetic mitral valve 2220 (orthe prosthetic mitral valve is advanced distally relative to the outersheath 2214 a) to expose the alignment element 2218 and a portion of theatrial skirt region 2222 on the prosthetic mitral valve 2220 whichallows the atrial skirt region 2222 to begin to partially radiallyexpand outward and flare open. Alignment element 2218 may include a pairof radiopaque markers 2218 a which facilitate visualization underfluoroscopy. The physician can then align the alignment element so thatthe radiopaque markers 2218 a are disposed on either side of theanterior mitral valve leaflet. Delivery device 2214 may be rotated inorder to help align the alignment element. The alignment element ispreferably situated adjacent the aortic root and between the fibroustrigones of the native anterior leaflet.

In FIG. 22D once alignment has been obtained, the sheath 2214 a isfurther retracted proximally, allowing radial expansion of the atrialskirt 2222 which flares outward to form a flange. Proximal retraction ofthe delivery device 2214 and prosthetic valve 2220 seat the atrial skirt2222 against an atrial surface adjacent the mitral valve 2206 therebyanchoring the prosthetic valve in a first position.

FIG. 22E shows that further proximal retraction of sheath 2214 a exposesand axially removes additional constraint from the prosthetic valve2220, thereby allowing more of the valve to self-expand. The annularregion 2224 expands into engagement with the mitral valve annulus andthe ventricular trigonal tabs 2226 and the posterior tab 2228 radiallyexpand. Portions of the ventricular skirt serve as deployment controlregions and prevent the entire ventricular skirt from expanding becausethey are still constrained. The tabs are captured between the anteriorand posterior mitral valve leaflets and the ventricular wall. Theposterior ventricular anchoring tab 2228 is preferably aligned in themiddle of the posterior mitral valve leaflet where there is an absenceof chordae attachments, and is passed over the posterior leaflet to seatbetween the posterior leaflet and the ventricular wall. The twoventricular trigonal anchoring tabs 2226 are positioned on either sideof the anterior leaflet with their heads positioned at the fibroustrigones. Slight rotation and realignment of the prosthesis can occur atthis time. As the prosthesis expands, the anterior trigonal tabs anchoragainst the fibrous trigones, capturing the native anterior leaflet andchordae between the tabs and the anterior surface of the prostheticvalve, and the posterior ventricular tab anchors between the ventricularwall and the posterior leaflet, capturing the posterior leaflet betweenthe posterior anchoring tab and the posterior surface of the prostheticvalve assembly.

FIG. 22F shows that further retraction of sheath 2214 a releases theventricular trigonal tabs and the posterior tab and the deploymentcontrol regions of the ventricular skirt 2230 are also released andallowed to radially expand outward against the native mitral valveleaflets.

This creates a sealing funnel within the native leaflets and helpsdirect blood flow through the prosthetic mitral valve. With thecommissures of the prosthesis still captured within the delivery system,very minor adjustments may still be made to ensure accurate positioning,anchoring and sealing. The prosthetic valve is now anchored in fourpositions. The anchor tabs 2232 are then released from the deliverydevice by retraction of an inner shaft, allowing the tabs to self-expandout of slots on the delivery catheter as previously discussed above andshown in FIG. 22G. The prosthetic valve is now implanted in thepatient's heart and takes over the native mitral valve. The deliverydevice 2214 may then be removed from the heart by proximally retractingit and removing it from the apex incision. The suture 2216 may then betied off, sealing the puncture site.

Transseptal Delivery Methods. FIGS. 23A-23G illustrate an exemplarymethod of transseptally delivering a prosthetic mitral valve. Thisembodiment may use any of the prosthetic valves described herein, andmay use any of the delivery devices described herein if modifiedappropriately. One of skill in the art will appreciate that relativemotion of the various shafts in the delivery system embodimentsdisclosed above may need to be reversed in order to accommodate atransseptal approach. FIG. 23A illustrates the general transseptalpathway that is taken with the delivery device passing up the vena cava2302 into the right atrium 2304. A transseptal puncture 2306 is createdthrough the atrial septum, often through the foramen ovale, so that thedevice may be passed into the left atrium 2308, above the mitral valve2310 and adjacent the left ventricle 2312. Transseptal techniques havebeen published in the patent and scientific literature, such as in U.S.Patent Publication No. 2004/0181238 to Zarbatany et al., the entirecontents of which are incorporated herein by reference.

In FIG. 23B a delivery device 2314 is passed over a guidewire GW throughthe vena cava 2302 into the right atrium 2306. The delivery device 2314is then transseptally passed through the atrial wall into the leftatrium 2308 adjacent the mitral valve 2310. The guidewire GW may bedisposed across the mitral valve 2310 in the left ventricle 2312. Thedistal tip of the delivery device typically includes a nose cone orother atraumatic tip to prevent damaging the mitral valve or adjacenttissue.

In FIG. 23C, the outer sheath 2214 a of the delivery device 2214 isretracted proximally relative to the prosthetic mitral valve 2319.Alternatively, a distal portion 2314 b of the delivery device 2214 maybe advanced distally relative to the prosthetic valve 2319 to expose thealignment element 2316 and a portion of the atrial skirt region 2318 onthe prosthetic mitral valve 2319 which allows the atrial skirt region2318 to begin to partially radially expand outward and flare open.Alignment element 2316 may include a pair of radiopaque markers 2316 awhich facilitate visualization under fluoroscopy. The physician can thenalign the alignment element so that the radiopaque markers 2316 a aredisposed on either side of the anterior mitral valve leaflet. Thealignment element is preferably situated adjacent the aortic root andbetween the fibrous trigones of the native anterior leaflet. Deliverydevice 2214 may be rotated in order to help align the alignment element.

In FIG. 23D once alignment has been obtained, the distal portion 2314 bis further advanced distally allowing radial expansion of the atrialskirt 2318 which flares outward to form a flange. Distally advancing thedelivery device 2214 and prosthetic valve 2319 seats the atrial skirt2318 against an atrial surface adjacent the mitral valve 2310 therebyanchoring the prosthetic valve in a first position.

FIG. 23E shows that further distal advancement of distal portion 2314 bexposes and axially removes additional constraint from the prostheticvalve 2319, thereby allowing more of the valve to self-expand. Theannular region 2320 expands into engagement with the mitral valveannulus and the ventricular trigonal tabs 2324 and the posterior tab2322 radially expand. Portions of the ventricular skirt serve asdeployment control regions since they remain constrained and thus theentire ventricular skirt cannot expand. The tabs are captured betweenthe anterior and posterior mitral valve leaflets and the ventricularwall. The posterior ventricular anchoring tab 2322 is preferably alignedin the middle of the posterior mitral valve leaflet where there is anabsence of chordae attachments, and is passed over the posterior leafletto seat between the posterior leaflet and the ventricular wall. The twoventricular trigonal anchoring tabs 2324 are positioned on either sideof the anterior leaflet with their heads positioned at the fibroustrigones. Slight rotation and realignment of the prosthesis can occur atthis time. As the prosthesis expands, the anterior trigonal tabs anchoragainst the fibrous trigones, capturing the native anterior leaflet andchordae between the tabs and the anterior surface of the prostheticvalve, and the posterior ventricular tab anchors between the ventricularwall and the posterior leaflet, capturing the posterior leaflet betweenthe posterior anchoring tab and the posterior surface of the prostheticvalve assembly.

FIG. 23F shows that further distal advancement of distal portion 2314 breleases the ventricular trigonal tabs and the posterior tab and theventricular skirt 2326 is also released and allowed to radially expandoutward against the native mitral valve leaflets without engaging theventricular wall. This creates a sealing funnel within the nativeleaflets and helps funnel blood flow through the prosthetic valve. Withthe commissures of the prosthetic valve still captured by the deliverysystem, very minor adjustments may still be made to ensure accuratepositioning, anchoring and sealing. The prosthetic valve is now anchoredin four positions. The anchor tabs 2328 are then released from thedelivery device by further advancement of an inner shaft, allowing thetabs to self-expand out of slots on the delivery catheter as previouslydiscussed above and shown in FIG. 23G. The prosthetic valve is nowimplanted in the patient's heart and takes over the native mitral valve.The delivery device 2314 may then be removed from the heart byproximally retracting it back through the atrial septum, and out of thevena cava.

FIG. 24 shows the prosthetic valve 2418 anchored in the mitral spaceafter transapical or transseptal delivery. Prosthetic valve 2418 ispreferably the prosthetic mitral valve illustrated in FIG. 8A, anddelivered by methods shown in FIGS. 22A-22G or FIGS. 23A-23G. Theprosthetic valve 2418 has radially self-expanded into engagement withthe mitral valve to anchor it in position without obstructing otherportions of the heart including the left ventricular outflow tract suchas aortic valve 2402. The anterior trigonal tabs 2408 (only 1 seen inthis view) and the posterior ventricular tab 2405 are radially expandedoutward from the rest of the ventricular skirt 2410 and the anteriorleaflet 2406 and posterior leaflet 2404 are captured between therespective tab and the ventricular skirt 2410 to form an anchor point.The ventricular skirt 2410 is also radially expanded outward to engageand press outwardly at least some of the chordae tendineae and papillarymuscles but preferably without pressing against the ventricular wall.The annular region 2416 is expanded radially outward to engage and pressagainst the mitral valve annulus, and the atrial skirt 2414 has alsoexpanded outwardly to form a flange that rests on top of the mitralvalve against the atrium. Thus, the prosthetic valve 2418 is anchored infour positions in the mitral space which prevents the prosthetic valvefrom migrating or dislodging during contraction of the heart. Moreover,using four anchor points lessens the anchoring pressure that is requiredto be applied in any given anchoring zone as compared to a prosthesisthat is anchored in only a single anchoring zone, or in any combinationof these four anchoring zones. The consequent reduction in radial forcerequired to be exerted against the native structures in each zoneminimizes the risk of obstruction or impingement of the nearby aorticvalve or aortic root caused by the displacement of the native mitralvalve apparatus. Valve leaflets 2420 form a tricuspid valve which openswith antegrade blood flow and closes with retrograde blood flow. Tab2412 on a tip of the commissures 2421 (best seen in FIG. 25) remainsfree after disengagement from the delivery device.

FIG. 25 illustrates the prosthetic valve 2418 of FIG. 24 anchored in themitral space and viewed from the left ventricle, looking upward towardthe atrium. As previously mentioned, the prosthetic valve 2418 may betransapically or transseptally delivered and is preferably theprosthetic mitral valve illustrated in FIG. 8A, delivered by methodsshown in FIGS. 22A-22G or FIGS. 23A-23G. This view more clearlyillustrates anchoring and engagement of the prosthetic mitral valve 2418with the adjacent tissue. For example, the three valve leaflets 2420forming the tricuspid valve are shown in the open position, allowingblood flow therepast. Additionally, the anterior trigonal tabs 2408 andthe posterior ventricular tab 2405 are shown radially expanded outwardinto engagement with the ventricular heart tissue 2425. The anteriorportion of the prosthetic valve in between anterior trigonal tabs 2408is approximately flat to match the corresponding flat anatomy aspreviously discussed above. The flat shape of the anterior portion ofthe prosthetic valve prevents the prosthetic valve from impinging on andobstructing adjacent anatomy such as the left ventricular outflow tractincluding the aortic valve. FIG. 25 also illustrates how the ventricularskirt 2410 expands radially outward against the native mitral valveleaflets.

Drug Delivery. Any of the prosthetic valves may also be used as a drugdelivery device for localized drug elution. The therapeutic agent may bea coated on the prosthetic valve, on the tissue covering the anchor, onboth, or otherwise carried by the prosthetic valve and controllablyeluted therefrom after implantation. Exemplary drugs includeanti-calcification drugs, antibiotics, anti-platelet aggregation drugs,anti-inflammatory drugs, drugs which inhibit tissue rejection,anti-restenosis drugs, anti-thrombogenic drugs, thrombolytic drugs, etc.Drugs which have these therapeutic effects are well known to those ofskill in the art.

Although the exemplary embodiments have been described in some detailfor clarity of understanding and by way of example, a variety ofadditional modifications, adaptations and changes may be clear to thoseof skill in the art. One of skill in the art will appreciate that thevarious features described herein may be combined with one another orsubstituted with one another. Hence, the scope of the present inventionis limited solely by the appended claims.

What is claimed is:
 1. A delivery system for delivering a prostheticcardiac valve to a patient's heart, said system comprising: an innerguidewire shaft having a lumen extending therethrough, the lumen adaptedto slidably receive a guidewire; a hub shaft disposed over the innerguidewire shaft, wherein the hub shaft comprises a plurality of slotsformed into an outer surface of the hub shaft to create a plurality ofdiscrete recessed regions and disposed adjacent a distal end thereof,the slots configured to receive and hold one or more portions of theprosthetic cardiac valve; a bell shaft slidably disposed over the hubshaft, the bell shaft having a distal section and a proximal section,wherein the distal section of the bell shaft has a diameter larger thana diameter of the proximal section of the bell shaft; a sheath slidablydisposed over the bell shaft, wherein the sheath is disposed over thelarger diameter distal section of the bell shaft during delivery of theprosthetic cardiac valve; and a handle comprising an actuator adapted toadvance and retract the bell shaft and the sheath.
 2. The system ofclaim 1, further comprising the prosthetic cardiac valve, wherein theprosthetic cardiac valve is housed in the sheath in a radially collapsedconfiguration.
 3. The system of claim 2, wherein proximal retraction ofthe sheath relative to the bell shaft removes a constraint from theprosthetic cardiac valve thereby allowing the prosthetic cardiac valveto self-expand into engagement with the patient's native heart tissue.4. The system of claim 2, wherein the prosthetic cardiac valve isreleasably coupled with the hub shaft, and wherein proximal retractionof the bell shaft relative to the hub shaft releases the prostheticcardiac valve therefrom.
 5. The delivery system of claim 1, wherein theprosthetic cardiac valve comprises: an anchor having an atrial skirt, anannular region, and a ventricular skirt; and a plurality of prostheticvalve leaflets, each of the leaflets having a first end and a free end,wherein the first end is coupled with the anchor and the free end isopposite of the first end, and wherein the prosthetic cardiac valve hasan open configuration in which the free ends of the prosthetic valveleaflets are disposed away from one another to allow antegrade bloodflow therepast, and a closed configuration in which the free ends of theprosthetic valve leaflets engage one another and substantially preventretrograde blood flow therepast.
 6. The system of claim 1, wherein theactuator mechanism comprises a rotatable wheel.
 7. The system of claim1, further comprising a tissue penetrating distal tip coupled to the hubshaft, wherein the tissue penetrating distal tip is adapted to passthrough and expand an incision in the patient's heart.
 8. The system ofclaim 1, further comprising a pin lock mechanism releasably coupled withthe handle, wherein the pin lock mechanism limits proximal retraction ofthe sheath.
 9. The system of claim 1, wherein the inner guidewire shaftremains stationary during actuation of the actuator mechanism.
 10. Thesystem of claim 1, wherein the hub shaft remains stationary duringactuation of the actuator mechanism.
 11. The system of claim 1, whereinproximal retraction of the sheath releases a portion of the prostheticcardiac valve from the delivery system.
 12. The system of claim 1,wherein the hub shaft is disposed coaxially over inner shaft.
 13. Thesystem of claim 12, wherein the hub shaft is disposed concentricallyover inner shaft.
 14. The system of claim 1, wherein the bell shaft isdisposed coaxially over hub shaft.
 15. The system of claim 14, whereinthe bell shaft is disposed concentrically over hub shaft.
 16. The systemof claim 1, wherein the sheath is disposed coaxially over the bellshaft.
 17. The system of claim 16, wherein the sheath is disposedconcentrically over the bell shaft.
 18. The system of claim 1, whereinthe handle is located near a proximal end of the delivery system.